The aim of this proposal is to evaluate sphingolipid metabolism in relation to normal development and to specific inherited human diseases (sphingolipidoses). The program will be divided into two parts: 1) fetal analyses, and 2) stdiessin leukodystrophy pathophysiology. Chemical and biochemical analyses of fetal neural tissues will evaluate changes occurring during gestation. These normal values will form the data base for evaluation of affected fetuses detected by prenatal diagnostic procedures. Developmental changes may expand our understanding of the dynamic processes occurring during the critical phases of growth and maturation of the human nervous system. Cultured skin fibroblasts will be utilized to investigate the pathophysiologies of two leukodystrophies, metachromatic leukodystrophy and globoid cell leukodystrophy (Krabbe's disease). The disorders are viewed as model systems which may provide information applicable to other sphingolipidoses.